Uteroglobin, first reported in 1968 as a steroid secreted in rabbit uterine fluid during early pregnancy, is a progesterone-regulated and progesterone-binding protein. There is evidence that indicates that uteroglobin is inversely correlated to neoplastic growth but its role to endometrial carcinogenesis is not known. Therefore we analyzed the expression of uteroglobin in 13 normal endometrium, 19 hyperplasia and 21 endometrial carcinoma samples and the relation to estrogen receptor-alpha (ER-alpha) and progesterone receptor (PR) by immunohistochemistry and Western blotting. We also analyzed the expression of uteroglobin in 15 menopausal women who received hormone replacement therapy (HRT). The expression of uteroglobin was higher during the secretory phase than in the proliferative phase; however, it was detected in endometrial hyperplasia as weakly as in the proliferative phase and decreased according to the loss of differentiation in endometrial carcinoma. The results were basically in accord with those for PR; however, the expression of uteroglobin was weak, though PR was most detected in endometrial hyperplasia. In menopausal endometrium, the group treated with estrogen plus progesterone exhibited higher expression of uteroglobin than the group treated only with estrogen. The evidence suggests that uteroglobin expression is regulated by progesterone in the normal endometrium but that the regulation by PR is lost in endometrial hyperplasia and carcinoma according to acquirement of tumorigenesis and that estrogen plus progesterone therapy reduces the risk for endometrial carcinoma by restoring uteroglobin.